chr8-4556794-T-C

Position:

• chr8-4556794-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.302+80548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,084 control chromosomes in the GnomAD database, including 2,301 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2301 hom., cov: 32)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.302+80548A>G		intron_variant		ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.302+80548A>G		intron_variant			XP_011533054.1
CSMD1	XM_017013731.2	c.302+80548A>G		intron_variant			XP_016869220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.302+80548A>G		intron_variant		5	NM_033225.6	ENSP00000489225	P4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24959 AN: 151966 Hom.: 2292 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.164 AC: 25016 AN: 152084 Hom.: 2301 Cov.: 32 AF XY: 0.165 AC XY: 12272 AN XY: 74336

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.157

Alfa AF: 0.132 Hom.: 2879

Bravo AF: 0.164

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.1
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1997137; hg19: chr8-4414316;